1、-內(nèi)酰胺類抗生素-Lactam antibiotics,Jingling Zhang and Kehua Jiao Medical school of Nankai University,-Lactam antibiotics,目的 掌握青霉素和頭孢霉素的抗菌作用?？咕V、適應(yīng)癥、不良反應(yīng)及其防治。青霉素G，各種半合成青霉素以及各種頭孢霉素的特點。了解兩類藥物的發(fā)展概況。,-Lactam antibiotics,內(nèi)容 青霉素G的理化性質(zhì)，抗菌譜，抗菌作用原理和作用特點。體內(nèi)過程和用藥方法。細(xì)菌耐藥性，過敏反應(yīng)及其防治。臨床用途。 普魯卡因青霉素G及芐星青霉素產(chǎn)生長效的原因及其臨床評價。以6-氨

2、基青霉烷酸為母核人工加上側(cè)鏈形成半合成青霉素。新青霉素具有耐青霉素酶特性。用于耐藥性金葡菌感染。,-Lactam antibiotics,廣譜青霉素氨芐青霉素和羧芐青霉素以及抗綠膿桿菌作用強的廣譜青霉素的抗菌作用特點及臨床用途。 頭孢霉素類為以7-氨基頭孢烷酸為主核加上不同側(cè)鏈的半合成抗菌素?；瘶?gòu)和抗菌作用原理與青霉素相似，抗菌譜較廣。常用的有頭孢菌素第一代，第二代，第三代等。各藥的特性和臨床應(yīng)用。,-Lactam antibiotics,Definition Classification Mechanism of action Resistance of microorganisms Pen

3、icillin,-Lactam antibiotics,Cephalosporins Other -lactam antibiotics -lactamase inhibitors,-Lactam antibiotics,Definition They are useful and frequently prescribed antibiotics that share a common structure and mechanism of action inhibition of synthesis of the bacterial peptidoglycan cell wall.,-Lac

4、tam antibiotics,Classification Penicillin Cephalosporins Other -lactam antibiotics -lactamase inhibitors,-Lactam antibiotics,Mechanism of action Inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis. The cell wall is a rigid outer layer that completely surroun

5、ds the cytoplasmic membrane.,-Lactam antibiotics,Penicillin-biding proteins (PBPs) catalyze the transpeptidase reaction that removes the terminal alanine to form a crosslink with a nearby peptide, which gives cell wall its structural rigidity.,粘肽,青霉素結(jié)蛋白,三維網(wǎng)狀結(jié)構(gòu),細(xì)胞壁,-內(nèi)酰胺類抗生素,-Lactam antibiotics,Type o

6、f PBPs (glycopeptide synthetase): 1A 9000 1B 9000 2 66000 3 60000 4, 5 and 6, 49000, 42000, 40000, ,-Lactam antibiotics,Penicillins are structural analogs of the natural D-Ala-D-Ala substrate. They are covalently bound by PBPs at the active site. After Penicillin has attached to the PBP, the transpe

7、ptidation reaction is inhibited, mucopeptide synthesis is blocked, and the cell dies.,-Lactam antibiotics,The exact mechanism responsible for cell death is not completely understood, but autolysins, bacterial enzymes that remodel and break down cell wall include the transpeptidases responsible for s

8、ynthesis of the peptidoglyca, are involved.,-Lactam antibiotics,Penicillins are bactericidal only if cells are actively growing and synthesizing cell wall. More effective on G+ than G. Kill the bacteria, but no any harmful to human body.,-Lactam antibiotics,Resistance of microorganisms Produce -lact

9、amase Trapping mechanism Change of PBPs Change permeability of membrane Lack of autolysins,-Lactam antibiotics,Penicillins the basic structure of penicillins consists of nucleus 6-aminopenicillanic acid and a side chain, containing a beta-lactam ring.,-Lactam antibiotics,Natural penicillin Penicilli

10、n G , benzylpenicillin Chemistry and characters high-yield , stabled , is the first choice in the treatment of the infection caused by susceptible bacteria.,-Lactam antibiotics,Antibacterial effect Antibacterial spectrum: narrow, G+, leptospira, Antibacterial activity: kill microorganism Mechanism o

11、f action: inhibits synthesis of bacterial cell wall,-Lactam antibiotics,Penicillins also removes or inactivates an inhibitor of the lytic enzymes (autolysin), resulting in lysis of microorganisms in an isotonic environment.,-Lactam antibiotics,Pharmacokinetics absorption of the drugs is complete and

12、 rapid , protein binding 56%, widely distributed in body fluids and tissues, high polar molecular and more in extracellular fluids,-Lactam antibiotics,Penicillin concentration in most tissues are equal to those in serum. It is excreted into sputum and milk. Penetration into the eye, the prostate, an

13、d the CNS is poor. With active inflammation of the meninges, penicillin are sufficient to kill susceptible bacteria.,-Lactam antibiotics,Penicillin is rapidly excreted by the kidneys into the urine, about 10% of renal excretion is by glomerular filtration and 90% by tubular secretion. Half-life from

14、 30 min to 10 hrs.,-Lactam antibiotics,Clinical uses It is the drug of first choice for treating the infections of the susceptible pathogens.,-Lactam antibiotics,The combination of an aminoglycoside is also necessary for bactericidal effects in enterococcal endocarditis.,-Lactam antibiotics,The simu

15、ltaneous administration of the relevant antitoxin is often necessary for the treatment of diphtheria and tetanus.,-Lactam antibiotics,Adverse effects Allergic reaction Typical anaphylactic shock (very rare, 0.05% recipients) Typical serum sickness type reactions,-Lactam antibiotics,A variety of skin

16、 rashes, oral lesions, fever, interstitial nephritis, eosinophilia, hemolytic anemia and other hematologic disturbances, and vasculitis.,-Lactam antibiotics,Prophylaxis and treatment Ask allergic history carefully Must make skin test, the injection of these drugs is made up before it is injected. As

17、 a number of these drugs are replaced, the skin test must be done again.,-Lactam antibiotics,After every injection, all of patients must be observed for half an hour, and the drugs for an emergency treatment are prepared at any time. Adrenaline (epinephrine) is the first drug for the treatment of an

18、aphylactic shock.,-Lactam antibiotics,Semisynthesis penicillins Orally penicillins Penicillins resistant to -lactamase Extended-spectrum penicillins Antipseudomonal penicillins Penicillins effect on G bacteria,-Lactam antibiotics,Cephalosporins The nucleus of the cephalosporins, 7-aminocephalosporan

19、ic acid, bears a close resemblance to 6-aminopenicillanic acid.,-Lactam antibiotics,The intrinsic antimicrobial activity of natural cephalosporins is low, but the attachment of various R1 and R2 groups has yielded drugs of good therapeutic activity and low toxicity.,7-aminocephalosporanic acid nucle

20、us (7-ACA),-Lactam antibiotics,Classification the first generation agents the second generations agents the third generation agents the fourth generation agents,the first generation agents,Characters : have powerful antimicrobial effects on G+ and staphylococcal that can produce -lactamase, less eff

21、ects on G, renal function decrease,Agents : cefalotin, cefazolin, cefradine, cefadroxil,the second generations agents,Characters : have more powerful against G, less effect on G+, a part of them are effective against anaerobe, have nephrotoxicity, Agents : cefuroxime, loracarbef,the third generation agents,Characters : have less activity against G+, much more activity against G, higher s